Vitamin E


Table of Contents
image Inhibition of transforming growth factor beta 1 induction by dietary vitamin E in unilateral ureteral obstruction in rats.
image Will the 'good fairies' please prove to us that vitamin E lessens human degenerative disease?.
image Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin treatment.
image Differential effect of alpha-tocopherol and ascorbate on oxidative injury induced in immune cells by thermal stress.
image Vitamin E prevents neutrophil accumulation and attenuates tissue damage in ischemic-reperfused human skeletal muscle.
image Inhibition of growth in oral squamous carcinoma cells by cyclopentenone prostaglandins: Comparison with chemotherapeutic agents.
image Vitamin E treatment in tardive dyskinesia.
image Vitamin E supplementation decreases lung virus titers in mice infected with influenza.
image Vitamin E and human health: Rationale for determining recommended intake levels.
image Vitamin E and cardiovascular protection in diabetes - Antioxidants may offer particular advantage in this high risk group.
image Early stage prostate cancer treated with radiation therapy: Stratifying an intermediate risk group.
image Vitamin E succinate inhibits proliferation of BT-20 human breast cancer cells: Increased binding of cyclin A negatively regulates E2F transactivation activity.
image Effect of vitamin E and taurine treatment on lipid peroxidation and antioxidant defense in perchloroethylene- induced cytotoxicity in mice.
image Lou Gehrig and amyotrophic lateral sclerosis: Is vitamin E to be revisited?.

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Inhibition of transforming growth factor beta 1
induction by dietary vitamin E in unilateral
ureteral obstruction in rats.

Kuemmerle NB Brandt RB Chan W Krieg RJ Chan JCM
Biochem Mol Med 1997 JUN;61(1):82-86
Kuemmerle NB, Virginia Commonwealth Univ, Med Coll Virginia,
Dept Pediat, Div Nephrol, Richmond,VA 23298 USA

Free radical species associated with bilateral ureteral obstruction (BUO) are considered important in the pathogenesis of the glomerular and tubulointerstitial injury in BUO rats, We seek to test the hypothesis that the use of an easily administered antioxidant, vitamin E, at sufficient plasma concentrations, can decrease this release of free oxygen radicals in kidney tissue and ameliorate the increase of the fibrogenic cytokine, transforming growth factor beta-1 (TGF beta-1). We used the unilateral ureteral obstruction (UUO) rat model, because the presence of the uninjured contralateral kidney provides a nonuremic internal milieu, in contrast to the uremic, acidotic, and hypercholesterolemic BUO model, Compared to sham controls, the UUO animals showed a dramatic increase in renal cortical TGF beta-1 mRNA, as quantitated by Northern blot analysis with cyclophilin internal standards. This increase in TGF beta-1 mRNA was reversed in UUO rats treated with vitamin E, The plasma malondialdehyde (MDA) concentration, an index of lipid peroxidation and an indirect index of free radical release, was significantly elevated in UUO animals compared to sham animals. The vitamin E-treated UUO animals showed a significant decrease in both plasma and renal cortical tissue MDA content, Taken together, these findings provide evidence of the important biological role of reactive free radical species in the tubulointerstitial injury of UUO and the novel role of vitamin E in modulating the mRNA of the fibrogenic TGF beta-1 in obstructive uropathy. (C) 1997 Academic Press.




Will the 'good fairies' please prove
to us that vitamin E lessens human
degenerative disease?

Diplock AT
Free Radical Res 1997;26(6):565-583
Diplock AT, Univ London, Guys Hosp, United Med
Dent Sch, Div Biochem ; Mol Biol,
Int Antioxidant Res Ctr, London SE1 9RT, ENGLAND

Recent research about the role of free radical derivatives of oxygen and nitrogen in biological systems has highlighted the possibility that antioxidants, such as vitamin El that prevent these processes in vitro may be capable of carrying out a similar function in living organisms in vivo. There is increasing evidence that free radical reactions are involved in the early stages, or sometimes later on, in the development of human diseases, and it is therefore of particular interest to inquire whether vitamin E and other antioxidants, which are found in the human diets, may be capable of lowering the incidence of these diseases. Put simply, the proposition is that by improving human diets by increasing the quantity in them of antioxidants, it might be possible to reduce the incidence of a number of degenerative diseases. Of particular significance to these considerations is the likely role of the primary fat-soluble dietary antioxidant vitamin E in the prevention of degenerative diseases such as arteriosclerosis, which is frequently the cause of consequent heart attacks or stroke, and prevention of certain forms of cancer, as well as several other diseases. Substantial evidence for this proposition now exists, and this review is an attempt to give a brief account of the present position. Two kinds of evidence exist; on the one hand there is very substantial basic science evidence which indicates an involvement of free radical events, and a preventive role for vitamin E, in the development of human disease processes. On the other hand, there is also a large body of human epidemiological evidence which suggests that incidence of these diseases is lowered in populations having a high level of antioxidants, such as vitamin E, in their diet, or who have taken steps to enhance their level of intake of the vitamin by taking dietary supplements. There is also some evidence which suggests that intervention with dietary supplements of vitamin E can result in a lowered risk of disease, in particular of cardiovascular disease, which is a major killer disease among the developed nations of the world. The intense interest in this subject recently has as its objective the possibility that, by making some simple alterations to dietary lifestyle, or by enhancing the intake of vitamin E by fortification of foods, or by dietary supplements, it may be possible to reduce substantially the risk of a large amount of common, highly disabling human disease. By this simple means, therefore it may be possible to improve substantially the quality of human life, in particular for people of advancing years.


Enhanced oxidizability of ubiquinol and
alpha-tocopherol during lovastatin treatment.

Palomaki A Malminiemi K MetsaKetela T
FEBS Lett 1997 JUN 30;410(2-3):254-258
Palomaki A, Kanta Hame Cent Hosp,
FIN 13530 Hameenlinna, FINLAND

A double-blinded, placebo-controlled cross-over trial was carried out with 27 hypercholesterolemic men with coronary heart disease. During the 6-week treatment period lovastatin (60 mg/day) decreased fasting serum LDL cholesterol by 45%, LDL phosp horus by 38% and apoB by 33%, Ubiquinol content diminished by 13% as measured per LDL phosphorus. When LDL was oxidized ex vivo with AMVN both LDL ubiquinol and a-tocopherol were exhausted faster after lovastatin treatment compared to placebo, by 24% (P & lt; 0.005) and 36% (P < 0.0001), respectively. Lag time in copper-induced oxidation of LDL decreased by 7% (P < 0.01), This suggests diminished antioxidant-dependent resistance of LDL to the early phase of oxidative stress. (C) 1997 Federation of Eu ropean Biochemical Societies.


Differential effect of alpha-tocopherol
and ascorbate on oxidative injury induced
in immune cells by thermal stress.

Franci O Ranfi F Scaccini C Amici A Merendino N Tommasi G Piccolella E
J Biol Regulat Homeost Agent 1996 APR-SEP;10(2-3):54-59
Piccolella E, Univ Roma La Sapienza, Dipartimento Biol Cellulare
Sviluppo, Via Apuli 1, I 00185 Rome, ITALY

As immune cells are often subjected to hyperthermia that can easily occur either after intense and/or prolonged exercise or during defense against pathogens, in this paper we analysed whether superoxide anion production occurred in lymphocytes exposed to high temperature and, consequently, if antioxidants could exert any protective function. The results demonstrated that an increase of superoxide anion was induced in rabbit lymphocytes exposed to 42 degrees C for 1h, although cell viability was not affected. However suppression of either Pokeweed mitogen (PWM)-driven cell proliferation, or immunoglobulin production or IL-2 synthesis was observed. To evaluate the capacity of antioxidants to restore the immune suppressed responses, two vitamins, a-tocopherol and ascorbic acid, were added to PWM-stimulated cultures following heat treatment The data demonstrated that a-tocopherol was able to totally abrogate the inhibitory effects mediated by thermal stress, while ascorbic acid did not give any protective results.


Vitamin E prevents neutrophil accumulation
and attenuates tissue damage in
ischemic-reperfused human skeletal muscle.

Formigli L Manneschi LI Tani A Gandini E Adembri
C Pratesi C Novelli GP Orlandini SZ
Histol Histopathol 1997 JUL;12(3):663-669
Formigli L, Univ Florence, Dept Human Anat
Histol, Viale Morgagni 85, I 50134 Florence, ITALY

Neutrophil accumulation and the consequent production of oxygen-derived free radicals are involved in the pathogenesis of Ischemia-Reperfusion syndrome. In this study we investigated whether a treatment with Vitamin E, which has antioxidant properties, could attenuate the tissue damage by interfering with the influx of neutrophils within the ischemic and reperfused human skeletal muscle. To this purpose, patients undergoing aortic cross-clamping during the surgical repair of aortic abdominal aneurysm were studied as a model of ischemia-reperfusion of the lower limb muscles. Muscle biopsies from the right femoral quadriceps of patients not receiving and receiving Vitamin E pretreatment before surgery were taken: a) after the induction of anaesthesia, as control samples, and b) after a period of ischemia followed by 30 min of reperfusion. The tissue samples were either routinely processed for morphological study and immunohistochemical analysis to detect an altered expression of specific endothelial adhesion proteins, such as E-selectin and ICAM-1. The results obtained showed that Vitamin E administration was able to prevent the accumulation of neutrophils within the ischemic and reperfused muscle. This beneficial effect of Vitamin E was due to its ability to hinder the expression of E-selectin and ICAM-1, molecules known to increase the adhesiveness of endothelium to circulating neutrophils. After treatment with Vitamin E a marked attenuation of the reperfusion injury was also evident. In conclusion, Vitamin E treatment may be considered a valuable tool for protection against the ischemia-reperfusion damage of human skeletal muscle..


Inhibition of growth in oral squamous
carcinoma cells by cyclopentenone prostaglandins:
Comparison with chemotherapeutic agents.

ElAttar TMA Virji AS
Prostagland Leuk Essent Fatty 1997 JUN;56(6):461-465
ElAttar TMA, Univ Missouri, Sch Dent,
Hormone Res Lab, Kansas City,MO 64108 USA

Four cyclopentenone prostaglandins (CPPGs) and PGE(2) caused significant dose-dependent inhibition in growth of human oral squamous carcinoma cells (SCC-15). The rank order of their potency was PGJ(2)>PGA(1)>16, 16-dimethyl PGA(1)>PGA(2) & gt;PGE(2). In a follow-up experiment it was found that the mean per cent inhibition in cell growth by PGJ(2) and Delta(12)-PGJ(2) at 10(-5) M was 61.22 and 63.81, while that of 5-fluorouracil and methotrexate was 36.67 and 38.86, respectively. Delta(12)-PGJ(2) and PGJ(2) induced significant dose-dependent inhibition in nuclear DNA synthesis (i.e. Cell proliferation). Combining vitamin E succinate with lower concentrations of CPPGs enhanced significantly their inhibitory effect on nuclear DNA synthesis of cancer cells.


Vitamin E treatment in tardive dyskinesia.

Dannon PN Lepkifker E Iancu I Ziv R Horesh N Kotler M
Hum Psychopharmacol Clin Exp 1997 MAY-JUN;12(3):217-220
Lepkifker E, Chaim Sheba Med Ctr,
Dept Psychiat, IL 52621 Tel Hashomer, ISRAEL

Sixteen patients with tardive dyskinesia were treated with vitamin E in an open trial of on-off-on design. Abnormal involuntary movement scale (AIMS) ratings were performed in every phase of the study. The patients exhibited a significant reductio n in their mean AIMS score during vitamin E treatment. Thus, this finding may suggest a possible role for vitamin E in the treatment of tardive dyskinesia. (C) 1997 by John Wiley Sons, Ltd.


Vitamin E supplementation decreases
lung virus titers in mice infected with influenza.

Hayek MG Taylor SF Bender BS Han SN Meydani
M Smith DE Eghtesada S Meydani SN
J Infect Dis 1997 JUL;176(1):273-276
Meydani SN, Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging,
Nutr Immunol Lab, Vasc Biol Lab,
Boston,MA 02111 USA

Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in you ng mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25- fold vs, 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic Tlymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.


Vitamin E and human health:
Rationale for determining recommended intake levels.

Weber P Bendich A Machlin LJ
Nutrition 1997 MAY;13(5):450-460
Weber P, Hoffmann La Roche Inc, Human Nutr Res Div,
45 Eisenhower Dr, Paramus,NJ 07652 USA

The recent literature provides strong evidence that vitamin E intakes much higher than the current recommendations can contribute to and/or improve human health. In fact, the available data indicate that at higher-than-current recommended intake levels, vitamin E affects several functions related to human health. For example, Vitamin E is required to protect polyunsaturated fatty acids (PUFAs) against auto-oxidation. The amount of vitamin E needed to protect PUFAs against oxidative damage is at least 0.4-0.8 mg vitamin E per gram PUFAs and may be in excess of 1.5 mg/g when diets contain higher-than- average levels of long-chain PUFAs. Based upon studies of vitamin E kinetics and metabolism a daily vitamin E intake of 135-150 IU is suggested. Important functions such as protection against oxidative damage, immune response, and the propensity of platelets to adhere to the vessel wall are related to vitamin E intakes. Vitamin E intake of 40 IU/d was the least amount demonstrated to inhibit low- density lipoprotein oxidation; a dose-dependent effect was seen up to 800 IU/d. Vitamin E intakes of at least 60 IU/d enhanced immune responses and intakes of 200 IU-400 IU/d decreased platelet adhesion to the vessel wall. Based upon the effects of modulating these functions, it is hypothesized that vitamin E plays a pivotal role in the prevention of cardiovascular diseases. Indeed, many observational studies have reported vitamin E to reduce the risk of cardiovascular disease. Recent intervention studies corroborate these findings. Of equal importance, there is a solid body of literature that demonstrates that these and much higher vitamin E intakes are safe. (C) Elsevier Science Inc. 1997.


Early stage prostate cancer
treated with radiation therapy:
Stratifying an intermediate risk group.

Lattanzi JP Hanlon AL Hanks GE
Int J Radiat Oncol Biol Phys 1997 JUN 1;38(3):569-573
Lattanzi JP, Fox Chase Canc Ctr, Dept Radiat Oncol,
7701 Burholme Ave, Philadelphia,PA 19111 USA

Purpose: This study identifies two early prostate cancer populations within the T1/T2AB, Gleason 2-7, pretreatment prostate specific antigen (PSA) 4-15 ng/ml grouping. By demonstrating different outcomes we may be able to more appropriately select a subgroup for whom adjuvant therapy trials or altered treatment techniques are indicated. Materials and Methods: One hundred forty-six patients with T1/T2AB, Gleason score 2-7, PSA 4-15 ng/ml prostate cancer were treated with external beam radiotherapy alone from November 1987 to October 1993. The median pretreatment PSA was 8.6 and the mean 8.7. Minimum follow-up was 2 years with a median of 38 months (mean 42 months, range 24-87). The median age was 70 years (range 58-83) and the median central axis dose delivered was 7240 cGy (mean 7273, range 6541-7895 cGy). Eleven patients received conventional radiotherapy while 135 were treated using conformal techniques. As there is evidence that a low PSA nadir is an early marker for long term biochemical control, time to post treatment PSA 1 ng/ml was actuarially analyzed by Gleason score, pretreatment PSA, radiation dose, stage, and the presence of perineural invasion. Pretreatment PSA was the only patient characteristic predictive of achieving a PSA level 1.0 ng/ml. Biochemical relapse free (bNED) control (non rising PSA) was then compared for patients above and below the approximate median pretreatment PSA level of 8 ng/ml. BNED control rates and the time to PSA 1.0 ng/ml were estimated using Kaplan- Meier methodology, and differences in bNED control and PSA 1.0 ng/ml according to PSA level were evaluated using the log-rank test. Results: Results from actuarial analysis revealed that pretreatment PSA was the only significant variable predictive of a PSA 1.0 ng/ml. Ninety-eight percent of patients with pretreatment PSA 8 achieved a PSA level 1.0 ng/ml within 3 years compared to 78% for patients with a PSA >8 ng/ml (p = 0.0003). BNED control for the two groups separated at a pretreatment PSA of 8 ng/ml confirms a favorable outcome, 88% bNED control at 5 years for 8 ng/ml and 74% for a pretreatment PSA greater than or equal to 8 ng/ml (p = 0.007 for overall curve comparison). Conclusion: For early prostate cancer patients (T1/T2AB, Gleason 2-7, pretreatment PSA 4-15) there is a significant break in bNED control following external beam radiation at a pretreatment PSA level of 8 ng/ml. Patients with pretreatment PSA 8 have a very favorable bNED response with radiation alone while those with a pretreatment PSA 8- 15 have a significant decrease in bNED response. The 27% failure rate at 5 years in the PSA 8-15 ng/ml patients may justify altered treatment techniques or clinical trials of adjuvant androgen deprivation in this group. (C) 1997 Elsevier Science Inc.



Vitamin E succinate inhibits proliferation
of BT-20 human breast cancer cells:
Increased binding of cyclin A negatively
regulates E2F transactivation activity.

Turley JM Ruscetti FW Kim SJ Fu T Gou FV BirchenallRoberts MC
Cancer Res 1997 JUL 1;57(13):2668-2675
BirchenallRoberts MC, NCI, Frederick Canc Res
Dev Ctr, Intramural Res & Support Program,
Sci Applicat Int Corp, Frederick,MD 21702 USA

Vitamin E succinate (VES) inhibited the proliferation of the estrogen receptor-negative human breast cancer cell line, BT-20, in the G(1) phase of the cell cycle. The E2F proteins are integral transcriptional components in the regulation of cell growth. Overexpression of E2F-1 blocked the ability of VES to inhibit BT-20 cell growth, suggesting that VES regulation of E2F-1 activity leads to growth arrest of BT-20 cells. VES, although having little effect on E2F-1 steady-state protein levels, decreased E2F- 1 phosphorylation and transactivation activity and increased cyclin A binding to E2F-1. GAL4-E2F-1 deletion mutant studies indicated that cyclin A negatively regulates E2F function. In VES-treated BT-20 cells, the cyclin A protein exhibited reduced kinase activity, which correlated with decreased steady-state levels and binding of cyclin-dependent kinase-2 to cyclin A and increased steady-state levels and binding of p21(cip1) to cyclin A and cyclin-dependent kinase-2. The functional consequence of the negative regulatory effect of VES on E2F-1 function was shown by the ability of VES to inhibit the transcriptional activation of an E2F-1 responsive gene, c- myc. These studies show that VES induces growth inhibition of BT-20 cells through a mechanism that involves cyclin A- negative regulation of E2F-mediated transcription.


Effect of vitamin E and taurine treatment
on lipid peroxidation and antioxidant defense
in perchloroethylene- induced cytotoxicity in mice.

Ebrahim AS Sakthisekaran D
J Nutr Biochem 1997 MAY;8(5):270-274
Sakthisekaran D, Univ Madras, Dept Med Biochem,
Taramani Campus, Madras 600113, Tamil Nadu, INDIA

Lipid peroxidation is thought to be an important event contributing to the toxicity of a variety of compounds like perchloroethylene (PER). PER is known to produce membrane damage through increased lipid peroxidation. An investigation of the relative importance of vitamin E and taurine in rendering protection to liver and kidney against PER induced cellular damage was performed. PER administered (3000 mg/kg body weight/day) mice were subjected to vitamin E (400 mg/kg body weight/day) and taurine (100 mg/kg body weight/day) treatment respectively for 15 days to study their individual effect on lipid peroxidative changes. A defective antioxidant defense system in PER administered mice was evidenced by the low level of enzymic antioxidants (SOD, CAT, GPx) and non- enzymic antioxidants (glutathione, ascorbic acid, total thiols, non-protein thiols, and vitamin E), with a simultaneous increase in lipid peroxidation (LPO) level. Vitamin E and taurine supplemented mice showed a marked reversal of these metabolic changes related to cellular damage caused by PER. Theses results suggest that PER induced cellular damage may be associated with lipid peroxidation and that can be effectively prevented by both vitamin E and taurine.


Lou Gehrig and amyotrophic lateral
sclerosis: Is vitamin E to be revisited?

Reider CR Paulson GW
Arch Neurol 1997 MAY;54(5):527-528
Reider CR, Ohio State Univ, Dept Neurol,
371 Mccampbell Hall, 1581 Dodd Dr,
Columbus,OH 43210 USA

Investigators are beginning to reexamine the use of vitamin E for the treatment of amyotrophic lateral sclerosis. Vitamin E was isolated in the 1920s, and the results of animal studies led rapidly to clinical use. Regrettably, vitamin E did not ameliorate the progression of amyotrophic lateral sclerosis for Lou Gehrig, but more recent advances may identify subpopulations that do respond to vitamin E.